Lipid-conjugates having a pharmacological activity of inhibiting the enzyme phospholipase A2 (PLA2, EC 3.1.1.4) are known in the prior art. Phospholipase A2 catalyzes the breakdown of phospholipids at the sn-2 position to produce a fatty acid and a lysophospholipid. The activity of this enzyme has been correlated with various cell functions, particularly with the production of lipid mediators such as eicosanoid production (prostaglandins, thromboxanes and leukotrienes), platelet activating factor and lysophospholipids.
Glycosaminoglycans (GAG) are macro-molecules that protect the cell membrane from attacks or stimuli by a multitude of extra-cellular agents such as: Free radicals (ROS), exogenous PLA2, interleukins and other inflammatory mediators, allergens, growth factors, and degrading enzymes or invasion-promoting enzymes (e.g., heparinase, collagenase, heparanase, hyaluronidase). GAG enrichment assists in protecting cells from damage.
Since their inception, lipid-conjugates have been subjected to intensive laboratory investigation in order to obtain a wider scope of protection of cells and organisms from injurious agents and pathogenic processes.
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinuses and upper airways.
CRS is now defined as a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks duration. The group of CRS disorders annually accounts as many as 22 million office visits and more than 500,000 emergency department visits in the U.S., according to some estimates. Annual CRS-related healthcare expenditures may reach as much as $3.5 billion.
Clinically, CRS is a heterogenous symptom complex, often resistant to medical therapy that is typically characterized by two or more of the following: mucopurulent drainage, nasal obstruction, facial pain/pressure and hyposmia/anosmia. CRS is clinically classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Often, CRSwNP is associated with nasal obstruction and smell loss, and CRSsNP is associated with facial pain/pressure and headaches.
Chronic rhinosinusitis with nasal polyps is a multifactorial disease, frequently associated with asthma and occasionally with aspirin sensitivity. Chronic rhinosinusitis with nasal polyps has mainly Th2 characteristics, with Eosinophilia and a typical cytokine profile.
Staphylococcus Aureus Superantigens (SAS) may be involved in the amplification of the inflammation and exacerbation of the disease. S. Aureus is the most common microorganism isolated from mucus adjacent to massive NP (60-70% of the cases), and IgE specific to SAS is often found in NP tissue. In addition, S. Aureus produce enterotoxins capable of acting on peripheral blood T lymphocytes stimulating cytokine production.